文献类型： 外文期刊

作者： Ji, Xingzhao ¹ ; Han, Lichao ⁴ ; Zhang, Weiying ¹ ; Sun, Lina ⁴ ; Xu, Shuai ⁴ ; Qiu, Xiaotong ⁴ ; Fan, Shihong ⁵ ; Li, Zhenjun ⁴ ;

作者机构： 1.Shandong First Med Univ, Dept Pulm & Crit Care Med, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China

2.Shandong First Med Univ, Shandong Key Lab Infect Resp Dis, Med Sci & Technol Innovat Ctr, Jinan, Shandong, Peoples R China

3.Shandong Acad Med Sci, Jinan, Shandong, Peoples R China

4.Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Inst Communicable Dis Control & Prevent, 155 Changbai Rd, Beijing 102206, Peoples R China

5.Yunnan Acad Agr Sci, Sericulture & Apiculture Res Inst, Mengzi 661100, Yunnan, Peoples R China

关键词： Nocardia farcinica; Dual RNA-seq; Virulence factor; Parkinson's disease; Microglia

期刊名称：BMC BIOLOGY （ 影响因子：7.364； 五年影响因子：8.641 ）

ISSN：

年卷期： 2022 年 20 卷 1 期

页码：

收录情况： SCI

摘要： Background Nocardia is a facultative intracellular pathogen that infects the lungs and brains of immunocompromised patients with consequences that can be fatal. The incidence of such infections is rising, immunocompetent individuals are also being infected, and there is a need to learn more about this neglected bacterial pathogen and the interaction with its human host. Results We have applied dual RNA-seq to assess the global transcriptome changes that occur simultaneously in Nocardia farcinica (N. farcinica) and infected human epithelial alveolar host cells, and have tested a series of mutants in this in vitro system to identify candidate determinants of virulence. Using a mouse model, we revealed the profiles of inflammation-related factors in the lung after intranasal infection and confirmed that nbtB and nbtS are key virulence genes for Nocardia infection in vivo. Regarding the host response to infection, we found that the expression of many histones was dysregulated during the infection of lung cells, indicating that epigenetic modification might play a crucial role in the host during Nocardia infection. In our mouse model, Nocardia infection led to neurological symptoms and we found that 15 of 22 Nocardia clinical strains tested could cause obvious PD-like symptoms. Further experiments indicated that Nocardia infection could activate microglia and drive M1 microglial polarization, promote iNOS and CXCL-10 production, and cause neuroinflammation in the substantia nigra, all of which may be involved in causing PD-like symptoms. Importantly, the deletion of nbtS in N. farcinica completely attenuated the neurological symptoms. Conclusions Our data contribute to an in-depth understanding of the characteristics of both the host and Nocardia during infection and provide valuable clues for future studies of this neglected human pathogen, especially those addressing the underlying causes of infection-related neurological symptoms.